Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI

<b>Background:</b> Although mTOR has long been regarded as a promising target for cancer treatment, the efficacy of mTOR inhibitors in most clinical trials has been rather limited. Nevertheless, their favorable safety profile has opened up opportunities for drug repurposing, even as thei...

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Main Authors: Ping Peng, Fan Shen, Bi Peng, Ziqi Chen, Lei Zhou, Xingjie Hao, Yuanhui Liu
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/4/839
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author Ping Peng
Fan Shen
Bi Peng
Ziqi Chen
Lei Zhou
Xingjie Hao
Yuanhui Liu
author_facet Ping Peng
Fan Shen
Bi Peng
Ziqi Chen
Lei Zhou
Xingjie Hao
Yuanhui Liu
author_sort Ping Peng
collection DOAJ
description <b>Background:</b> Although mTOR has long been regarded as a promising target for cancer treatment, the efficacy of mTOR inhibitors in most clinical trials has been rather limited. Nevertheless, their favorable safety profile has opened up opportunities for drug repurposing, even as their potential applications across various diseases remain largely unexplored. <b>Methods:</b> We performed an MR-PheWAS analysis across 1431 phenotypes to explore drug repurposing opportunities. We analyzed GWAS data of 452 plasma metabolites, 731 immune traits, and 412 gut microbiota to uncover potential mechanisms for the causal link between the mTOR gene and body mass index (BMI). <b>Results:</b> A causal link between mTOR gene expression and BMI has been established. Additionally, mTOR-related vulnerabilities associated with BMI, including alterations in metabolites, immune traits, and gut microbiota, were identified. <b>Conclusions:</b> The identified causal relationship between mTOR and BMI suggests novel potential non-cancer applications for mTOR inhibitors.
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series Biomedicines
spelling doaj-art-8d57bc38fa77442db07a5961cc872d4e2025-08-20T02:17:20ZengMDPI AGBiomedicines2227-90592025-03-0113483910.3390/biomedicines13040839Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMIPing Peng0Fan Shen1Bi Peng2Ziqi Chen3Lei Zhou4Xingjie Hao5Yuanhui Liu6Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaNursing Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China<b>Background:</b> Although mTOR has long been regarded as a promising target for cancer treatment, the efficacy of mTOR inhibitors in most clinical trials has been rather limited. Nevertheless, their favorable safety profile has opened up opportunities for drug repurposing, even as their potential applications across various diseases remain largely unexplored. <b>Methods:</b> We performed an MR-PheWAS analysis across 1431 phenotypes to explore drug repurposing opportunities. We analyzed GWAS data of 452 plasma metabolites, 731 immune traits, and 412 gut microbiota to uncover potential mechanisms for the causal link between the mTOR gene and body mass index (BMI). <b>Results:</b> A causal link between mTOR gene expression and BMI has been established. Additionally, mTOR-related vulnerabilities associated with BMI, including alterations in metabolites, immune traits, and gut microbiota, were identified. <b>Conclusions:</b> The identified causal relationship between mTOR and BMI suggests novel potential non-cancer applications for mTOR inhibitors.https://www.mdpi.com/2227-9059/13/4/839mTOR inhibitorgenetic evidencerepurposing opportunityBMI
spellingShingle Ping Peng
Fan Shen
Bi Peng
Ziqi Chen
Lei Zhou
Xingjie Hao
Yuanhui Liu
Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI
Biomedicines
mTOR inhibitor
genetic evidence
repurposing opportunity
BMI
title Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI
title_full Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI
title_fullStr Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI
title_full_unstemmed Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI
title_short Genetic Evidence Supporting the Repurposing of mTOR Inhibitors for Reducing BMI
title_sort genetic evidence supporting the repurposing of mtor inhibitors for reducing bmi
topic mTOR inhibitor
genetic evidence
repurposing opportunity
BMI
url https://www.mdpi.com/2227-9059/13/4/839
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